© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
17β-Estradiol stimulates expression of endothelial and inducible NO synthase in rat myocardium in-vitro and in-vivo
aMedizinische Poliklinik, University of Bonn, Bonn, Germany
bCardiovascular Research Institute Maastricht, Maasricht, The Netherlands
cInstitut für Physiologie II, University of Bonn, Bonn, Germany
* Corresponding author. Tel.: +49-228-287-2233; fax: +49-228-287-2266 c.grohe{at}uni-bonn.de
Objectives: NO production has been attributed to play a major role in cardiac diseases such as cardiac hypertrophy and cardiac remodeling after myocardial infarction which display significant gender-based differences. Therefore we assessed the effect of 17β-estradiol (E2) on estrogen receptor (ER) 
and β and endothelial and inducible NO synthase in neonatal and adult rat cardiomyocytes. Methods: The presence of ER and ERβ was demonstrated by immunofluorescence and western blot analysis as well as the expression pattern of inducible NO synthase (iNOS) and endothelial NOS (eNOS) in isolated cardiomyocytes from neonatal and adult rats. Furthermore, regulation of myocardial iNOS and eNOS expression by estrogen was evaluated in the myocardium from ovariectomized or sham-operated adult Wistar-Kyoto rats. Results: Incubation with E2 led to translocalization of the ER into the nucleus and increased receptor protein expression. E2 stimulated expression of iNOS and eNOS in both neonatal and adult cardiac myocytes. Coincubation with the pure anti-estrogen ICI 182.780 inhibited upregulation of ER and NOS expression. In ovariectomized rats myocardial iNOS and eNOS protein levels were significantly lower compared to sham-operated female animals. Conclusion: Taken together, these results show that E2 stimulates the expression of iNOS/eNOS in neonatal and adult cardiomyocytes in-vivo and in-vitro. These novel findings provide a potential mechanism of how estrogen may modulate NOS expression and NO formation in the myocardium.
KEYWORDS Estrogen receptor , β; Inducible/endothelial NO synthase; Cardiac myocytes
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